Janet Kim

Date of Award

11-10-2006

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Bruce G Haffty

Abstract

The purpose of this study was to assess the prognostic significance and clinical correlations of cyclooxgenase-2 expression (COX) in a cohort of patients treated with radiation (RT) for post-mastectomy chest wall relapse (PMCWR). Between 1975 and 1999, 113 patients were treated for isolated PMCWR. All patients were treated with biopsy and/or excision of the CWR followed by RT. Median follow-up was 10 years. All clinical data including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy were entered into a computerized database. Paraffin-embedded CWR specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0-3+. A score of 2-3+ was considered positive. Overall survival from original diagnosis for the entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years. The distant metastasis-free survival rate after CWR was 40% at 10 years. Local-regional control of disease was achieved in 79% at 10 years after CWR. COX was considered positive in 13 of 38 cases. COX was inversely correlated with ER (p= .045) and PR (p = .028), and positively correlated with HER-2/neu (p =.003). COX was also associated with a shorter time to PMCWR. The distant metastasis-free rate for COX negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2 positive patients (p = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative (p = 0.003). Outcome following RT for PMCWR is relatively poor. Positive COX correlated with other markers of poor outcome including a shorter time to local relapse, negative ER/PR and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for PMCWR.

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This is an Open Access Thesis.

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